Syndecan-4 is a key maestro of stomach cancer progression with patient’s prognosis association
Abstract
PFIZER RESEARCH AWARDS 2024
Scientific Background
Stomach cancer is often a silent disease, frequently diagnosed at advanced disease stage, and with still limited therapeutic options. Our research group and several others have shown that gastric cancer cells display aberrant cell surface glycosylation signatures, which hold promise not only as diagnosis biomarkers but also as novel clinical targets.
In recent years, a growing amount of scientific evidence has highlighted that protein post-translation modifications, such as glycosylation, harbour significant relevance and functional impact in determining cancer cell biological behaviour. The glycoconjugates (molecules modified with covalently linked carbohydrate chains) expressed at every cell surface glycocalyx are essential players within the tumour microenvironment. These glycosylated molecules display pivotal roles in defining extracellular matrix (ECM) biochemical and biophysical properties and shaping cancer cell communication in the tumour but also at distant sites. Among these molecular regulators, heparan sulfate proteoglycans (HSPGs), particularly Syndecan-4 (SDC4), are emerging as critical players in tumour development, cell migration, invasion, and extracellular communication [1-3].
Syndecans (SDCs) comprise a family of four type-I transmembrane HSPGs. SDCs are highly abundant at the cell surface and act in cooperation with different transmembrane receptors and ECM molecules with multiple functions in cell signalling, adhesion, proliferation, migration, apoptosis, and differentiation. The SDCs expression profile, and their glycosylation features, have been frequently described as aberrantly altered in various cancers, including gastrointestinal tumours. Moreover, we have recently reported that the heparan sulfate (HS) cellular balance shapes cancer cell motility features and contributes to gastric cancer cells aggressiveness [2].
Lately, proteoglycans have been pinpointed as important partners in extracellular vesicle (EVs) mediated communication in the tumour microenvironment. Particularly, SDCs have been implied in EVs biogenesis, cargo selection and secretion, as well as for defining cancer cell-derived EVs uptake by recipient cells, ultimately fine-tuning tumour dissemination.
